Clinical significance of cancer specific methylation of the CDO1 gene in small bowel cancer

• Published in: PloS one Vol. 14; no. 1; p. e0211108
• Main Authors: Kojima, Keita, Nakamura, Takatoshi, Ooizumi, Yosuke, Igarashi, Kazuharu, Tanaka, Toshimichi, Yokoi, Keigo, Ishii, Satoru, Nishizawa, Nobuyuki, Katoh, Hiroshi, Kosaka, Yoshimasa, Sato, Takeo, Watanabe, Masahiko, Yamashita, Keishi
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 24.01.2019; Public Library of Science (PLoS)
• Subjects: Aged; Analysis; Biology and life sciences; Cancer; Carcinogenesis; Carcinogens; Cell Line, Tumor; Chemotherapy; Clinical significance; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - enzymology; Colorectal Neoplasms - genetics; Colorectal Neoplasms - mortality; Colorectal Neoplasms - pathology; Cysteine dioxygenase; Cysteine Dioxygenase - genetics; Cysteine Dioxygenase - metabolism; Deoxyribonucleic acid; Development and progression; Disease-Free Survival; DNA; DNA Methylation; DNA, Neoplasm - genetics; DNA, Neoplasm - metabolism; Esophagus; Female; Gallbladder; Gastric cancer; Gastrointestinal cancer; Gastrointestinal Stromal Tumors - enzymology; Gastrointestinal Stromal Tumors - genetics; Gastrointestinal Stromal Tumors - mortality; Gastrointestinal Stromal Tumors - pathology; Genes; Genetic aspects; Humans; Leiomyosarcoma - enzymology; Leiomyosarcoma - genetics; Leiomyosarcoma - mortality; Leiomyosarcoma - pathology; Lymphoma; Lymphoma - enzymology; Lymphoma - genetics; Lymphoma - mortality; Lymphoma - pathology; Male; Medical prognosis; Medicine; Medicine and Health Sciences; Middle Aged; Mucosa; Mutation; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Patients; Physical Sciences; Prognosis; Proteins; R&D; Research & development; Research and Analysis Methods; Retrospective Studies; Small intestine; Small intestine cancer; Stomach cancer; Surgery; Survival Rate; Tissues; Tumors; Variance analysis; United States > US; Japan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0211108

Although small bowel cancer (SBC) is extremely rare, its prognosis is poor, and molecular mechanism of the SBC development remains unclear. The aim of our study is to elucidate whether DNA methylation of the promoter region of the cancer-specific methylation gene, cysteine dioxygenase 1 (CDO1), contributes to the carcinogenic process in SBC. The study group comprised patients with 53 patients with SBC, 107 colorectal cancer (CRC), and other rare tumors of the small intestine such as 4 malignant lymphomas, 2 leiomyosarcomas, and 9 gastrointestinal stromal tumors. We analyzed the extent of methylation in each tissue using quantitative TaqMan methylation-specific PCR for CDO1. Significantly higher CDO1 methylation was observed in cancer tissues compared with non-cancerous mucosa of the small intestine (ROC = 0.96). Among the various clinicopathological factors, positive correlation of CDO1 methylation with tumor diameter was observed (R = 0.31, p = 0.03), and the CDO1 methylation level was a possible prognostic factor for relapse-free survival (p = 0.09). Compared with CRC, SBC had a significantly poorer prognosis (p = 0.007) and displayed a significantly higher CDO1 methylation level (p < 0.0001). Intriguingly, especially in pStage I/II, there were robust prognostic difference between SBC and CRC (p = 0.08 / p < 0.0001), which may reflect CDO1 methylation status (p = 0.02 / p = 0.001). Among small bowel tumors, CDO1 methylation in SBC was higher in order of malignant lymphoma, cancer, and leiomyosarcoma/GIST (p = 0.002) by ANOVA. The CDO1 gene shows extremely cancer-specific hypermethylation, and it can be a prognostic marker in SBC.